Q92574 (TSC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hamartin

Alternative name(s):
Tuberous sclerosis 1 protein

Gene names

Name:	TSC1
Synonyms:	KIAA0243, TSC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1164 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Ref.9 Ref.10
Subunit structure	Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with DOCK7. Interacts with TBC1D7. Ref.6 Ref.7 Ref.8 Ref.11 Ref.12 Ref.13
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note: At steady state found in association with membranes. Ref.6
Tissue specificity	Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.
Domain	The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.
Post-translational modification	Phosphorylation at Ser-505 does not affect interaction with TSC2. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Involvement in disease	Defects in TSC1 are the cause of tuberous sclerosis type 1 (TSC1) [MIM:191100]. It is an autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. TS1C is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical symptoms can range from benign hypopigmented macules of the skin to profound mental retardation with intractable seizures to premature death from a variety of disease-associated causes. Ref.20 Ref.22 Ref.24 Ref.25 Ref.27 Defects in TSC1 may be a cause of focal cortical dysplasia of Taylor balloon cell type (FCDBC) [MIM:607341]. FCDBC is a subtype of cortical displasias linked to chronic intractable epilepsy. Cortical dysplasias display a broad spectrum of structural changes, which appear to result from changes in proliferation, migration, differentiation, and apoptosis of neuronal precursors and neurons during cortical development. Ref.28

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy Tumor suppressor
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of Rho GTPase activity Inferred from direct assay. Source: UniProtKB cell cycle arrest Traceable author statement. Source: Reactome cell-matrix adhesion Inferred from mutant phenotype. Source: UniProtKB insulin receptor signaling pathway Traceable author statement. Source: Reactome negative regulation of TOR signaling cascade Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB negative regulation of translation Inferred from mutant phenotype. Source: UniProtKB positive regulation of focal adhesion assembly Inferred from direct assay. Source: UniProtKB protein stabilization Inferred from direct assay. Source: UniProtKB rRNA export from nucleus Inferred from mutant phenotype. Source: UniProtKB regulation of phosphoprotein phosphatase activity Inferred from mutant phenotype. Source: UniProtKB regulation of stress fiber assembly Inferred from direct assay. Source: UniProtKB
Cellular component	TSC1-TSC2 complex Inferred from direct assay Ref.7. Source: UniProtKB cell cortex Inferred from direct assay. Source: UniProtKB lamellipodium Inferred from direct assay. Source: UniProtKB membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	chaperone binding Inferred from physical interaction Ref.8. Source: UniProtKB protein N-terminus binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKB	O14920	3	EBI-1047085,EBI-81266
MAPK14	Q16539	2	EBI-1047085,EBI-73946
NGFRAP1	Q00994	5	EBI-1047085,EBI-741753
TSC2	P49815	7	EBI-1047085,EBI-396587

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1164	1164	Hamartin		PRO_0000065651
Regions
	Coiled coil	721 – 997	277	Potential
	Compositional bias	1034 – 1037	4	Poly-Gly
	Compositional bias	1038 – 1043	6	Poly-Ser
Amino acid modifications
	Modified residue	394	1	Phosphoserine By similarity
	Modified residue	505	1	Phosphoserine Ref.11 Ref.15 Ref.16 Ref.17 Ref.18
	Modified residue	511	1	Phosphoserine Ref.16
	Modified residue	598	1	Phosphoserine Ref.16
	Modified residue	1102	1	Phosphoserine Ref.14 Ref.17
Natural variations
	Natural variant	51	1	E → D in TSC1; could be a polymorphism.		VAR_009397
	Natural variant	68	1	H → R in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.29		VAR_054386
	Natural variant	72	1	L → P in TSC1. Ref.22		VAR_054387
	Natural variant	158	1	F → C in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.29		VAR_054388
	Natural variant	190	1	R → S.		VAR_009398
	Natural variant	191	1	L → H in TSC1; could be a polymorphism.		VAR_009399
	Natural variant	198 – 199	2	NF → I in TSC1.		VAR_009400
	Natural variant	206	1	H → D in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. Ref.29		VAR_054389
	Natural variant	216	1	F → L in a bladder tumor; diffuse punctate cytoplasmic distribution in aminoacid-starved conditions; does not affect interaction with TSC2. Ref.29		VAR_054390
	Natural variant	224	1	M → R in TSC1; could be a polymorphism.		VAR_009401
	Natural variant	322	1	M → T. Ref.20 Ref.21 Ref.23 Ref.24 Ref.26 Corresponds to variant rs1073123 [ dbSNP | Ensembl ].		VAR_009402
	Natural variant	417	1	T → I in TSC1; could be a polymorphism; does not affect interaction with TSC2. Ref.24 Ref.26 Ref.29		VAR_009403
	Natural variant	500	1	R → Q in TSC1. Ref.27		VAR_054391
	Natural variant	577	1	E → D. Ref.26		VAR_009404
	Natural variant	586 – 589	4	CKIP → S in TSC1.		VAR_009405
	Natural variant	587	1	K → R. Ref.1 Ref.21		VAR_009406
	Natural variant	654	1	Q → E in TSC1. Ref.24		VAR_009407
	Natural variant	726	1	A → E in TSC1. Ref.20		VAR_009408
	Natural variant	732	1	H → Y in FCDBC; could be a polymorphism. Ref.20 Ref.21 Ref.23 Ref.28		VAR_009409
	Natural variant	809	1	E → Q. Ref.23		VAR_009410
	Natural variant	829	1	S → R. Ref.26		VAR_009411
	Natural variant	899	1	T → S in TSC1. Ref.24		VAR_009412
	Natural variant	1035	1	G → S. Ref.20 Ref.21		VAR_009413
	Natural variant	1108	1	G → S. Ref.21		VAR_009414

Sequences

	Sequence		Length	Mass (Da)
	Q92574 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: EF15509385C7AACC	FASTA	1,164	129,767
	10 20 30 40 50 60 MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI 70 80 90 100 110 120 LTTLQEPHDK HLLDRINEYV GKAATRLSIL SLLGHVIRLQ PSWKHKLSQA PLLPSLLKCL 130 140 150 160 170 180 KMDTDVVVLT TGVLVLITML PMIPQSGKQH LLDFFDIFGR LSSWCLKKPG HVAEVYLVHL 190 200 210 220 230 240 HASVYALFHR LYGMYPCNFV SFLRSHYSMK ENLETFEEVV KPMMEHVRIH PELVTGSKDH 250 260 270 280 290 300 ELDPRRWKRL ETHDVVIECA KISLDPTEAS YEDGYSVSHQ ISARFPHRSA DVTTSPYADT 310 320 330 340 350 360 QNSYGCATST PYSTSRLMLL NMPGQLPQTL SSPSTRLITE PPQATLWSPS MVCGMTTPPT 370 380 390 400 410 420 SPGNVPPDLS HPYSKVFGTT AGGKGTPLGT PATSPPPAPL CHSDDYVHIS LPQATVTPPR 430 440 450 460 470 480 KEERMDSARP CLHRQHHLLN DRGSEEPPGS KGSVTLSDLP GFLGDLASEE DSIEKDKEEA 490 500 510 520 530 540 AISRELSEIT TAEAEPVVPR GGFDSPFYRD SLPGSQRKTH SAASSSQGAS VNPEPLHSSL 550 560 570 580 590 600 DKLGPDTPKQ AFTPIDLPCG SADESPAGDR ECQTSLETSI FTPSPCKIPP PTRVGFGSGQ 610 620 630 640 650 660 PPPYDHLFEV ALPKTAHHFV IRKTEELLKK AKGNTEEDGV PSTSPMEVLD RLIQQGADAH 670 680 690 700 710 720 SKELNKLPLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN QLLYERFKRQ QHALRNRRLL 730 740 750 760 770 780 RKVIKAAALE EHNAAMKDQL KLQEKDIQMW KVSLQKEQAR YNQLQEQRDT MVTKLHSQIR 790 800 810 820 830 840 QLQHDREEFY NQSQELQTKL EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES 850 860 870 880 890 900 VQQQMEFLNR QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELEK NRSHVLQQTQ 910 920 930 940 950 960 RLDTSQKRIL ELESHLAKKD HLLLEQKKYL EDVKLQARGQ LQAAESRYEA QKRITQVFEL 970 980 990 1000 1010 1020 EILDLYGRLE KDGLLKKLEE EKAEAAEAAE ERLDCCNDGC SDSMVGHNEE ASGHNGETKT 1030 1040 1050 1060 1070 1080 PRPSSARGSS GSRGGGGSSS SSSELSTPEK PPHQRAGPFS SRWETTMGEA SASIPTTVGS 1090 1100 1110 1120 1130 1140 LPSSKSFLGM KARELFRNKS ESQCDEDGMT SSLSESLKTE LGKDLGVEAK IPLNLDGPHP 1150 1160 SPPTPDSVGQ LHIMDYNETH HEHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34." van Slegtenhorst M.A., de Hoogt R., Hermans C., Nellist M., Janssen B., Verhoef S., Lindhout D., van den Ouweland A.M.W., Halley D.J.J., Young J., Burley M., Jeremiah S., Woodward K., Nahmias J., Fox M., Ekong R., Osborne J., Wolfe J. , Povey S., Snell R.G., Cheadle J.P., Jones A.C., Tachataki M., Ravine D., Sampson J.R., Reeve M.P., Richardson P., Wilmer F., Munro C., Hawkins T.L., Sepp T., Ali J.B.M., Ward S., Green A.J., Yates J.R.W., Kwiatkowska J., Henske E.P., Short M.P., Haines J.H., Jozwiak S., Kwiatkowski D.J. Science 277:805-808(1997) [PubMed: 9242607] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-587.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed: 9039502] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 466-1164. Tissue: Bone marrow.
[5]	"A silent mutation 1947 T-->C in exon 15 of TSC1 in Chinese." Fang L., Wang N., Murong S.X., Wu Z.Y., Lin M.T. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 568-586.
[6]	"Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles." Plank T.L., Yeung R.S., Henske E.P. Cancer Res. 58:4766-4770(1998) [PubMed: 9809973] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TSC2.
[7]	"Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products." van Slegtenhorst M.A., Nellist M., Nagelkerken B., Cheadle J.P., Snell R.G., van den Ouweland A.M.W., Reuser A., Sampson J.R., Halley D.J.J., van der Sluijs P. Hum. Mol. Genet. 7:1053-1057(1998) [PubMed: 9580671] [Abstract] Cited for: INTERACTION WITH TSC2.
[8]	"Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin." Nellist M., van Slegtenhorst M.A., Goedbloed M., van den Ouweland A.M.W., Halley D.J.J., van der Sluijs P. J. Biol. Chem. 274:35647-35652(1999) [PubMed: 10585443] [Abstract] Cited for: INTERACTION WITH TSC2.
[9]	"Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling." Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., Blenis J. Proc. Natl. Acad. Sci. U.S.A. 99:13571-13576(2002) [PubMed: 12271141] [Abstract] Cited for: FUNCTION.
[10]	"Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity." Li Y., Inoki K., Guan K.-L. Mol. Cell. Biol. 24:7965-7975(2004) [PubMed: 15340059] [Abstract] Cited for: FUNCTION.
[11]	"Phosphorylation and binding partner analysis of the TSC1-TSC2 complex." Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J., Luider T.M. Biochem. Biophys. Res. Commun. 333:818-826(2005) [PubMed: 15963462] [Abstract] Cited for: PHOSPHORYLATION AT SER-505, MASS SPECTROMETRY, INTERACTION WITH DOCK7 AND TSC2.
[12]	"TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase." Chong-Kopera H., Inoki K., Li Y., Zhu T., Garcia-Gonzalo F.R., Rosa J.L., Guan K.-L. J. Biol. Chem. 281:8313-8316(2006) [PubMed: 16464865] [Abstract] Cited for: INTERACTION WITH TSC2.
[13]	"Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex." Nakashima A., Yoshino K., Miyamoto T., Eguchi S., Oshiro N., Kikkawa U., Yonezawa K. Biochem. Biophys. Res. Commun. 361:218-223(2007) [PubMed: 17658474] [Abstract] Cited for: INTERACTION WITH TBC1D7.
[14]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1102, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[15]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, MASS SPECTROMETRY. Tissue: Platelet.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505; SER-511 AND SER-598, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505 AND SER-1102, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]	"Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis." Jones A.C., Daniells C.E., Snell R.G., Tachataki M., Idziaszczyk S.A., Krawczak M., Sampson J.R., Cheadle J.P. Hum. Mol. Genet. 6:2155-2161(1997) [PubMed: 9328481] [Abstract] Cited for: VARIANT TSC1 GLU-726, VARIANTS THR-322; TYR-732 AND SER-1035. Tissue: Peripheral blood.
[21]	"Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance." Kwiatkowska J., Jozwiak S., Hall F., Henske E.P., Haines J.L., McNamara P., Braiser J., Wigowska-Sowinska J., Kasprzyk-Obara J., Short M.P., Kwiatkowski D.J. Ann. Hum. Genet. 62:277-285(1998) [PubMed: 9924605] [Abstract] Cited for: VARIANTS THR-322; ARG-587; TYR-732; SER-1035 AND SER-1108. Tissue: Blood.
[22]	"Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations." Benit P., Kara-Mostefa A., Hadj-Rabia S., Munnich A., Bonnefont J.-P. Hum. Mutat. 14:428-432(1999) [PubMed: 10533069] [Abstract] Cited for: VARIANT TSC1 PRO-72.
[23]	"Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis." Niida Y., Lawrence-Smith N., Banwell A., Hammer E., Lewis J., Beauchamp R.L., Sims K., Ramesh V., Ozelius L. Hum. Mutat. 14:412-422(1999) [PubMed: 10533067] [Abstract] Cited for: VARIANTS THR-322; TYR-732 AND GLN-809. Tissue: Blood and Lymphoblast.
[24]	"Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex." Zhang H., Nanba E., Yamamoto T., Ninomiya H., Ohno K., Mizuguchi M., Takeshita K. J. Hum. Genet. 44:391-396(1999) [PubMed: 10570911] [Abstract] Cited for: VARIANTS TSC1 ILE-417; GLU-654 AND SER-899, VARIANT THR-322. Tissue: Blood.
[25]	"Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation." Van Slegtenhorst M.A., Verhoef S., Tempelaars A., Bakker L., Wang Q., Wessels M., Bakker R., Nellist M., Lindhout D., Halley D.J.J., van den Ouweland A.M.W. J. Med. Genet. 36:285-289(1999) [PubMed: 10227394] [Abstract] Cited for: VARIANTS TSC1, VARIANTS. Tissue: Peripheral blood.
[26]	"Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations." Yamashita Y., Ono J., Okada S., Wataya-Kaneda M., Yoshikawa K., Nishizawa M., Hirayama Y., Kobayashi E., Seyama K., Hino O. Am. J. Med. Genet. 90:123-126(2000) [PubMed: 10607950] [Abstract] Cited for: VARIANTS THR-322; ILE-417; ASP-577 AND ARG-829. Tissue: Peripheral blood leukocyte.
[27]	"Tuberous sclerosis type 1: three novel mutations detected in exon 15 by a combination of HDA and TGGE." Hass J., Mayer K., Rott H.-D. Hum. Mutat. 16:88-88(2000) [PubMed: 10874311] [Abstract] Cited for: VARIANT TSC1 GLN-500.
[28]	"Focal cortical dysplasia of Taylor's balloon cell type: mutational analysis of the TSC1 gene indicates a pathogenic relationship to tuberous sclerosis." Becker A.J., Urbach H., Scheffler B., Baden T., Normann S., Lahl R., Pannek H.W., Tuxhorn I., Elger C.E., Schramm J., Wiestler O.D., Bluemcke I. Ann. Neurol. 52:29-37(2002) [PubMed: 12112044] [Abstract] Cited for: VARIANT FCDBC TYR-732.
[29]	"Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms." Pymar L.S., Platt F.M., Askham J.M., Morrison E.E., Knowles M.A. Hum. Mol. Genet. 17:2006-2017(2008) [PubMed: 18397877] [Abstract] Cited for: VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417, CHARACTERIZATION OF VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF013168 mRNA. Translation: AAC51674.1. AL445645 Genomic DNA. Translation: CAH72112.1. CH471090 Genomic DNA. Translation: EAW88021.1. AC002096 Genomic DNA. No translation available. D87683 mRNA. Translation: BAA13436.1. AF234185 Genomic DNA. Translation: AAF61948.1.
IPI	IPI00022043.
PIR	T03814.
RefSeq	NP_000359.1. NM_000368.4. NP_001155898.1. NM_001162426.1. NP_001155899.1. NM_001162427.1.
UniGene	Hs.370854.
3D structure databases
ProteinModelPortal	Q92574.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92574. 32 interactions.
MINT	MINT-1534928.
STRING	Q92574.
PTM databases
PhosphoSite	Q92574.
Polymorphism databases
DMDM	9297077.
Proteomic databases
PRIDE	Q92574.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298552; ENSP00000298552; ENSG00000165699. ENST00000440111; ENSP00000394524; ENSG00000165699.
GeneID	7248.
KEGG	hsa:7248.
UCSC	uc004cca.1. human.
Organism-specific databases
CTD	7248.
GeneCards	GC09M135766.
H-InvDB	HIX0008496.
HGNC	HGNC:12362. TSC1.
HPA	CAB011568. CAB012481.
MIM	191100. phenotype. 605284. gene. 607341. phenotype.
neXtProt	NX_Q92574.
Orphanet	65683. Isolated focal cortical dysplasia. 538. Lymphangioleiomyomatosis. 805. Tuberous sclerosis.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000014148.
HOGENOM	HBG445246.
HOVERGEN	HBG012559.
InParanoid	Q92574.
OMA	GFDSPFY.
OrthoDB	EOG4S4PFD.
PhylomeDB	Q92574.
Enzyme and pathway databases
Pathway_Interaction_DB	pi3kciaktpathway. Class I PI3K signaling events mediated by Akt. mtor_4pathway. mTOR signaling pathway.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q92574.
Bgee	Q92574.
CleanEx	HS_TSC1.
Genevestigator	Q92574.
GermOnline	ENSG00000165699. Homo sapiens.
Family and domain databases
InterPro	IPR007483. Hamartin. [Graphical view]
KO	K07206.
PANTHER	PTHR15154. Hamartin. 1 hit.
Pfam	PF04388. Hamartin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	28341.
SOURCE	Search...

Entry information

Entry name

TSC1_HUMAN

Accession

Primary (citable) accession number: Q92574
Secondary accession number(s): Q5VVN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.